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Objective: Primary care providers need effective strategies for substance use screening and brief counseling of adolescents. We examined the effects of a new computer-facilitated screening and provider brief advice (cSBA) system., Methods: We used a quasi-experimental, asynchronous study design in which each site served as its own control. From 2005 to 2008, 12- to 18-year-olds arriving for routine care at 9 medical offices in New England (n = 2096, 58% females) and 10 in Prague, Czech Republic (n = 589, 47% females) were recruited. Patients completed measurements only during the initial treatment-as-usual study phase. We then conducted 1-hour provider training, and initiated the cSBA phase. Before seeing the provider, all cSBA participants completed a computerized screen, and then viewed screening results, scientific information, and true-life stories illustrating substance use harms. Providers received screening results and "talking points" designed to prompt 2 to 3 minutes of brief advice. We examined alcohol and cannabis use, initiation, and cessation rates over the past 90 days at 3-month follow-up, and over the past 12 months at 12-month follow-up., Results: Compared with treatment as usual, cSBA patients reported less alcohol use at follow-up in New England (3-month rates 15.5% vs 22.9%, adjusted relative risk ratio [aRRR] = 0.54, 95% confidence interval 0.38-0.77; 12-month rates 29.3% vs 37.5%, aRRR = 0.73, 0.57-0.92), and less cannabis use in Prague (3-month rates 5.5% vs 9.8%, aRRR = 0.37, 0.17-0.77; 12-month rates 17.0% vs 28.7%, aRRR = 0.47, 0.32-0.71)., Conclusions: Computer-facilitated screening and provider brief advice appears promising for reducing substance use among adolescent primary care patients.